Michael J. Meredith
Ph.D., Virginia Polytechnic Institute and State University, 1977
Associate Professor, Department of Oral Molecular Biology, School of Dentistry
Joint Associate Professor, Cell and Developmental Biology
Research in this labortatory continues to focus on the role of glutathione (GSH) in defense against free radical and oxidant challenge and the regulation of cellular metabolism. Three projects are currently under way. 1) GSH in the pathology of Alzheimer's and Parkinson's disease: The recent studies have shown that mitochondrial DNA mutation in complex I (Parkinson's) and IV (Alzheimer's) genes initiate increase free radical production. Because glutathione peroxidase is the only peroxide detoxication system within the mitochondria, we are investigating the metabolism of glutathione in cell culture models of these diseases. 2) GSH and apoptosis: Expression of the anti-appaptosis protein Bcl-2 has been shown to cause increased glutathione levels. We are examining the mechanism of the glutathione elevation and the role of GSH in cultured cells expressing this protein.3) Studies of the regulation of glutathione by oxidant challenge continue at the level of transcriptional regulation
- Meredith, M.J., Cusick, C.L., Soltaninassab, S., Sekhar, K.S., Lu, S., and
Freeman, M.L. (1998) Expression of Bcl-2 increases intracellular glutathione
by inhibiting methionine-dependent GSH efflux. Biochem. Biophys. Res.
Commun. 248,458-463.
- M. B. Yatvin, M. J. Meredith, M. S. Jangi and M. A. Shenoy (2000) Strategies for Targeting and Release of active Anti-cancer and Anti-microbial Drugs from Lipophilic Prodrugs and from Microparticles. Cell. Mol Biol. Letters, 5,119-132
- Soltaninassab, S.R.,Konjeti, R., Borrelli, M.J, Zhi-Qi Xu, Meredith, M.J, Domann, F.E., and Freeman Michael L. (2000) Proteosome-dependent signaling induces the synthesis of the anti-oxidant glutathione. Biochem. Biophys. Res. Commun., 270, 311-317.
- Konjeti R. Sekhar, Douglas R. Spitz, Stephanie Harris, Trung T. Nguyen 1 , Michael J.Meredith, Jeffrey T. Holt, David Guis, Lawrence J. Marnett, Marshall L. Summar and Michael L. Freeman. Indomethacin-Induced Redox Sensitive Expression of gamma-Glutamylcysteine Synthetase is Mediated by MEK-1 and Nrf2. (in press)J. Biol. Chem.